3(S)-Hydroxymethyl-4-benzylmorpholine

106973-36-8

101376-25-4

General procedure for the synthesis of (S)-(4-benzylmorpholin-3-yl)methanol from (R)-4-benzyl-5-oxo-3-morpholinecarboxylic acid: to a stirred solution of (R)-4-benzyl-5-oxo-3-morpholinecarboxylic acid (17.7 g, 75.3 mmol) in tetrahydrofuran (THF, 300 mL) was added triethylamine (NEt3, 7.3 g, 10.0 mL, 72.0 mmol). The reaction mixture was cooled to 0 °C and dimethyl sulfide borane complex (BH3-Me2S, 10 M THF solution, 45.0 mL, 450.0 mmol) was slowly added. After heating and refluxing the reaction mixture for 12 h, it was cooled to room temperature and the excess borane was quenched by slow addition of methanol (MeOH) at 0 °C. The reaction mixture was concentrated in vacuum and the resulting white solid was dissolved in ethyl acetate (EtOAc, 120 mL) and washed with aqueous sodium hydroxide (20% v/v, 2 x 100 mL). The organic phase was extracted with 2M aqueous hydrochloric acid (2 x 150mL). The acidic aqueous phases were combined, alkalized to pH 14 with solid sodium hydroxide, and back-extracted with ethyl acetate (2 × 150 mL). The organic phases were combined, washed with brine (150 mL), dried over anhydrous magnesium sulfate (MgSO4), filtered and concentrated in vacuum to give (S)-(4-benzylmorpholin-3-yl)methanol (13.5 g, 87% yield) as a clear oil, which did not need to be further purified. δH(CDCl3) 7.29-7.16 (5H, m), 4.05 (1H, d, J = 12.8 Hz), 3.88 (1H, dd, J=11.5 Hz and J=4.5 Hz), 3.78 (1H, m), 3.70-3.53 (2H, m), 3.51-3.40 (2H, m), 3.20 (1H, d, J=13.2 Hz), 2.68 (1H, dt, J=12.1 Hz and J=2.8 Hz). 2.48 (1H, m), 2.27 (1H, m), 2.20-2.15 (1H, br.s).